DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Compound IC-14
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, which reads on Claims 1-25, in the reply filed on 1 May 2026 is acknowledged. The claimed species was searched, with no prior art retrieved. The search was expanded to have variable R3 as phenyl with any substitution, with no prior art retrieved. The search was expanded to variables Ra and Rb as all options, with no prior art retrieved. The search was expanded to all of variable R3 with no prior art retrieved. All of variable R7 was then searched, with prior art retrieved. The search was then stopped (See STN Search, Search Notes).
Claims 1-25, submitted on 1 May 2026, represent all claims currently under consideration.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Priority
This application is a 371 of PCT/GB2022/051370, filed 27 May 2022, which claims priority to GB 2107612.0, filed 27 May 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The effective filing date is 27 May 2021.
Claim Objections
Claims 1-7 and 10-12 are objected to because of the following informalities: Each instance of (1-6C), (3-8C), (1-2C), (2-6C), (3-6C), (1-4C), (1-3), and (4-6C) should be replaced with C1-C6, for example. Appropriate correction is required.
Claim 3 is objected to because of the following informalities: There is a superfluous “or” in between 5- or 6-membered heteroaryl. Appropriate correction is required.
Claim 4 is objected to because of the following informalities: There is a superfluous “or” in between 6-membered heteroaryl and 6-membered heterocyclyl. Appropriate correction is required.
Claim 21 is objected to because of the following informalities: There are no commas in between each of the claimed compounds. Appropriate correction is required.
Claims 4-20 and 22-25 objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claims. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 2 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims 1 and 2 are indefinite because there is no “or” or “and” prior to 5- to 12-memberd heterocyclyl, and no “or” or “and” prior to 5- to 12-membered heterocyclyl in the substitution portion.
Claim 3 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 3 depends on Claim 2, which recites the limitation that variable "R3 can be 5- to 12-membered heterocycle or heteroaryl", however, Claim 3 states that variable R3 can be any fused heteroaryl or fused heterocycle in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 depends on Claim 2, which recites the limitation that variable "R3 can be 5- to 12-membered heterocycle or heteroaryl", however, Claim 3 states that variable R3 can be any fused heteroaryl or fused heterocycle. As Claim 3 claims any fused heteroaryl or fused heterocycle, this is broader than Claim 2, and thus does not further limit this claim. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Brem (WO 2017/093727; Publication Date: 8 June 2017).
Brem discloses compounds, in particular, indole derivatives that function as inhibitors of bacterial metallo-beta lactamase. The invention relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of a bacterial infection (Abstract). The invention provides a compound or salt or solvate thereof, for use in the treatment of a bacterial infection (Paragraph 0009). Another aspect of the invention provides a compound as defined herein, or a salt or solvate thereof, in combination with a suitable antibacterial agent, for use in the treatment of a bacterial infection (Paragraph 0010). Another aspect provides a pharmaceutical composition comprising a compound of the invention and one or more pharmaceutically acceptable excipients (Paragraph 0011). The invention provides a method of treating a bacterial infection in a patient in need of such treatment, comprising administering a therapeutically effective amount of a compound of the invention, or a pharmaceutical composition as defined herein, in combination with a suitable antibacterial agent (Paragraph 0015). The present invention provides the use of a compound in combination with a suitable antibacterial agent, for the treatment of a bacterial infection (Paragraph 0016). The present invention relates to a compound of formula I or a pharmaceutically acceptable salt thereof
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wherein A1 through A4 are selected from C or N, with the proviso that only one or two of A1 through A4 can be N; R1 is selected from hydrogen, optionally substituted alkyl, or optionally substituted aryl, R2 is selected
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, wherein RA is selected from halo, cyano, nitro, or a group of the formula -Y2-X2-Z2, wherein
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R3 is selected from hydrogen, halo, cyano, hydroxyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, or heterocycle, which are optionally substituted by one or more RB, wherein R4 through R6 can be hydrogen, and R7 is selected from hydrogen, halo, cyano, nitro, hydroxy, or a group -Y7-X7-Z7 wherein
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(Paragraph 0048). Particular compounds of the invention that are disclosed include Example 61 (Page 68)
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, which has variable R2 as COOH, variable R3 as substituted phenyl, and analogous variable R7 as CH2OCH3 with both variables Ra and Rb as hydrogen ; Example 62 (Page 69)
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, which has variable R2 as COOH, variable R3 as substituted phenyl, and analogous variable R7 as CH2O-Phenyl with both variables Ra and Rb as hydrogen; Example 81 (Page 73)
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, which has variable R2 as COOH, variable R3 as substituted phenyl, and analogous variable R7 as CH2O-Phenyl with both variables Ra and Rb as hydrogen; Example 83 (Page 74)
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, which has variable R2 as COOH, variable R3 as substituted phenyl, and analogous variable R7 as CH2O-Phenyl with both variables Ra and Rb as hydrogen; Example 84 (Page 74)
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, which has variable R2 as COOH, variable R3 as substituted phenyl, and analogous variable R7 as CH2O-Phenyl with both variables Ra and Rb as hydrogen; and Example 108 (Page 80)
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, which has . All compounds show moderate to high inhibitory potency against VIM-2, IMP-1, and NDM-1 as demonstrated in Table 1 (Page 143), with pIC50 values all greater than 5.5, and several above 7, indicating potency in the low micromolar to low nanomolar range against three different metallo-beta lactamases.
Brem does not disclose a compound wherein at least one of analogous variable Ra or Rb is not hydrogen and is replaced by a C1-C6 alkyl group. However, the artisan would not expect the insertion of a C1-C6 alkyl group into this position to significantly alter the chemical properties of the cited compounds due to the close chemical structure of the resulting compound (See MPEP § 2144.09 I). The artisan would not expect inserting a single alkyl chain into these compounds to significantly alter the inhibitory capacity of the resulting compound. These compounds are shown to be potent inhibitors of three different metallo-beta-lactamases, providing the artisan both a motivation to select these compounds for modification, and a reasonable expectation that modifying these compounds by inserting an alkyl chain would not significantly change the inhibitory capacity of the resulting compound.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. 11,439,622 (Patent Date: 13 September 2022) (‘622).
Claim 1 of ‘622 is directed to a compound of Formula I
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wherein A1 through A4 are each C, R1 is hydrogen, R2 is COOH, R3 is optionally substituted aryl, cycloalkyl, heteroaryl, or heterocycle, R4 through R6 are each hydrogen, and R7 is selected from cyano, hydroxy, or a group -Y7-X7-Z7, wherein
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. Claim 5 is directed to several specific compounds, including
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,
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,
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,
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,
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, and
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. These compounds differ from what is claimed in the examined application as they have both analogous variables Ra and Rb as hydrogen. The claims at issue are not identical but are not patentably distinct because of the close chemical structure between the cited compounds and what is claimed in the examined application. The artisan would not expect the insertion of a C1-C6 alkyl group into this position to significantly alter the chemical properties of the cited compounds due to the close chemical structure of the resulting compound (See MPEP § 2144.09 I). The artisan would not expect inserting a single alkyl chain into these compounds to significantly alter the inhibitory capacity of the resulting compound. These compounds are shown to be potent inhibitors of three different metallo-beta-lactamases, providing the artisan both a motivation to select these compounds for modification, and a reasonable expectation that modifying these compounds by inserting an alkyl chain would not significantly change the inhibitory capacity of the resulting compound.
Allowable Subject Matter
Claim 21 is objected to, but otherwise allowable.
The following is an examiner’s statement of reasons for allowance: There is no prior art which teaches, suggests, or provides motivation for, the specific compounds of Claim 21 (See STN Search, Search Notes). The closest prior art comes from Brem (WO 2017/093727, cited above). The compounds which are claimed have moieties such as
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, heteroaromatic rings,
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,
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, spirocycles including those claimed in examined Claim 13, and
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in the variable R7 position. Brem does not disclose the use of moieties such as this in their compounds, and there would be no motivation, nor reasonable expectation of success, in choosing to modify the compounds of Brem to include these groups as they have not been shown to be effective in inhibiting metallo-beta-lactamases.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Claims 1-3 are rejected.
Claim 21 is objected to, but otherwise allowable.
Claims 4-20 and 22-25 are objected to for improper multiple dependencies and have not been further examined on the merits.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.M.R./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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